The basal ganglia are important components of the motor system. Diseases of the basal ganglia cause impaired voluntary movement, abnormal involuntary movements, or both. It is generally agreed that the basal ganglia function in concert with cerebral cortical mechanisms in the control of many aspects of behavior. A large portion of the basal ganglia-thalmocortical circuitry is devoted to the control of movement. Despite substantial advances in understanding the contributions of these circuits to motor control, there is still no consensus as to how the basal ganglia output influences cortical motor areas. The proposed experiments will investigate the function of basal ganglia-thalamocortical circuits in the control of limb movement in primates. Selective inactivation of basal ganglia output neurons in globus pallidus, pars interna (GPi) will be combined with recording neuronal activity in cortical targets of that output while monkeys perform a wrist movement task. We have hypothesized that a key function of the basal ganglia in voluntary movement is to facilitate the desired motor pattern and to simultaneously inhibit potentially competing motor patterns so that they do not interfere with the one that has been selected. We will test this overall hypothesis in 2 specific aims. We will determine how movement-related neuronal signals in supplementary motor area (SMA) and primary motor cortex (MC) change after reversible inactivation of GPi and how those signal changes relate to the resulting motor impairment. We will also determine if GPi activity correlates with suppression of an "automatic" movement response and whether inactivation of GPi prevents suppression of that response and interferes with performance of a movement in the opposite direction from the "automatic" response. These experiments will directly test the effect on cortical motor physiology of inactivating the basal gangia output for limb movements. They will provide important new information on how the basal ganglia interact with motor areas of cerebral cortex. This results of this project will enhance understanding of normal basal ganglia function in motor control and will provide important clues to the pathophysiology of movement disorders resulting from basal ganglia diseases. Better understanding of these mechanisms will have potential significant impact on development of better therapies for those movement disorders.